title: Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.
abstract: This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.
authors.affiliation: Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA. flmeyske@uci.edu
authors.forename: Frank L
authors.initials: FL
authors.lastname: Meyskens
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Curt
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.forename: Gary
authors.initials: G
authors.lastname: Gordon
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Herberman
authors.forename: Olivera
authors.initials: O
authors.lastname: Finn
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: Samir N
authors.initials: SN
authors.lastname: Khleif
authors.forename: Caroline C
authors.initials: CC
authors.lastname: Sigman
authors.forename: Eva
authors.initials: E
authors.lastname: Szabo
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods*; D002986:Clinical Trials as Topic; D017277:Drug Approval; D004345:Drug Industry / Q000379:methods; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008297:Male; D008495:Medical Oncology / Q000379:methods; D009369:Neoplasms / Q000517:prevention & control; D010349:Patient Compliance; D012306:Risk
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor